TY - JOUR
T1 - Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia
AU - Yu, Minzhong
AU - Sturgill-Short, Gwen
AU - Ganapathy, Preethi
AU - Tawfik, Amany
AU - Peachey, Neal S.
AU - Smith, Sylvia B.
N1 - Funding Information:
This study was supported by NIH grant R01 EY12830 , the Foundation Fighting Blindness , Challenge Grants from Research to Prevent Blindness , and the VA Medical Research Service .
PY - 2012/3
Y1 - 2012/3
N2 - Homocysteine is an amino acid required for the metabolism of methionine. Excess homocysteine is implicated in cardiovascular and neurological disease and new data suggest a role in various retinopathies. Mice lacking cystathionine-beta-synthase (cbs -/-) have an excess of retinal homocysteine and develop anatomical abnormalities in multiple retinal layers, including photoreceptors and ganglion cells; heterozygous (cbs +/-) mice demonstrate ganglion cell loss and mitochondrial abnormalities in the optic nerve. The purpose of the present study was to determine whether elevated homocysteine, due to absent or diminished cbs, alters visual function. We examined cbs -/- (3 weeks) and cbs +/- mice (5, 10, 15, 30 weeks) and results were compared to those obtained from wild type (WT) littermates. Conventional dark- and light-adapted ERGs were recorded, along with dc-ERG to assess retinal pigment epithelial (RPE) function. The visual evoked potential (VEP) was used to assess transmission to the visual cortex. The amplitudes of the major ERG components were reduced in cbs -/- mice at age 3 weeks and VEPs were delayed markedly. These findings are consistent with the early retinal disruption observed anatomically in these mice. In comparison, at 3 weeks of age, responses of cbs +/- mice did not differ significantly from those of WT mice. Functional abnormalities were not observed in cbs +/- mice until 15 weeks of age, at which time amplitude reductions were noted for the ERG a- and b-wave and the light peak component, but not for other components generated by the RPE. VEP implicit times were delayed in cbs +/- mice at 15 and 30 weeks, while VEP amplitudes were unaffected. The later onset of functional defects in cbs +/- mice is consistent with a slow loss of ganglion cells reported previously in the heterozygous mutant. Light peak abnormalities indicate that RPE function is also compromised in older cbs +/- mice. The data suggest that severe elevations of homocysteine are associated with marked alterations of retinal function while modest homocysteine elevation is reflected in milder and delayed alterations of retinal function. The work lays the foundation to explore the role of homocysteine in retinal diseases such as glaucoma and optic neuropathy.
AB - Homocysteine is an amino acid required for the metabolism of methionine. Excess homocysteine is implicated in cardiovascular and neurological disease and new data suggest a role in various retinopathies. Mice lacking cystathionine-beta-synthase (cbs -/-) have an excess of retinal homocysteine and develop anatomical abnormalities in multiple retinal layers, including photoreceptors and ganglion cells; heterozygous (cbs +/-) mice demonstrate ganglion cell loss and mitochondrial abnormalities in the optic nerve. The purpose of the present study was to determine whether elevated homocysteine, due to absent or diminished cbs, alters visual function. We examined cbs -/- (3 weeks) and cbs +/- mice (5, 10, 15, 30 weeks) and results were compared to those obtained from wild type (WT) littermates. Conventional dark- and light-adapted ERGs were recorded, along with dc-ERG to assess retinal pigment epithelial (RPE) function. The visual evoked potential (VEP) was used to assess transmission to the visual cortex. The amplitudes of the major ERG components were reduced in cbs -/- mice at age 3 weeks and VEPs were delayed markedly. These findings are consistent with the early retinal disruption observed anatomically in these mice. In comparison, at 3 weeks of age, responses of cbs +/- mice did not differ significantly from those of WT mice. Functional abnormalities were not observed in cbs +/- mice until 15 weeks of age, at which time amplitude reductions were noted for the ERG a- and b-wave and the light peak component, but not for other components generated by the RPE. VEP implicit times were delayed in cbs +/- mice at 15 and 30 weeks, while VEP amplitudes were unaffected. The later onset of functional defects in cbs +/- mice is consistent with a slow loss of ganglion cells reported previously in the heterozygous mutant. Light peak abnormalities indicate that RPE function is also compromised in older cbs +/- mice. The data suggest that severe elevations of homocysteine are associated with marked alterations of retinal function while modest homocysteine elevation is reflected in milder and delayed alterations of retinal function. The work lays the foundation to explore the role of homocysteine in retinal diseases such as glaucoma and optic neuropathy.
KW - Electrophysiology
KW - Electroretinogram
KW - Mouse
KW - Optic nerve
KW - Retina
KW - Retinal degeneration
KW - Retinal function
KW - Visual evoked potential
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U2 - 10.1016/j.exer.2011.12.011
DO - 10.1016/j.exer.2011.12.011
M3 - Article
C2 - 22197750
AN - SCOPUS:84862803353
SN - 0014-4835
VL - 96
SP - 124
EP - 131
JO - Experimental eye research
JF - Experimental eye research
IS - 1
ER -